Obesity and other clinical endpoints in steroid-sensitive nephrotic syndrome

Abstract

Sirs,We read with great interest the article of Foster et al.[1] on risk factors for glucorticoid-induced obesity in children with steroid-sensitive nephrotic syndrome (SSNS). The prevalence of obesity in patients with remote SSNS was high with 20%, however, not significantly different from the prevalence in the reference group. We have recently reported a comprehensive long-term study on 42 adults treated for childhood SSNS, providing also a detailed analysis of growth [2]. The median BMI was 23 kg/m 2 ; in five women and three men the BMI was >25, and only one female was obese, with a BMI of 31.4. No correlation was found between height and weight in adulthood and the cumulative prednisone dose or duration of prednisone administration. The epidemic of being overweight and obese appears to be more prevalent in the US than in some European countries. We suggest to add to the conclusion of Foster's report that the prevalence of persistent obesity in children with SSNS is also correlated with the local prevalence or epidemic of obesity in the healthy reference group.Also, other clinical endpoints seem to differ in various geographical areas. Hegarty et al.[3] reported a high prevalence of bone fractures in adults treated with steroids for childhood SSNS in the UK: Of the 24 male and 10 female subjects, 19 (79.2%) and 3 (30%), respectively, had suffered a total of 43 self-reported fractures. In contrast, only 2 (5%) of the 42 patients in our study had sustained a single bone fracture although our patients were not given calcium or vitamin D supplements.We propose that the long-term outcome and clinical endpoints in steroid-sensitive idiopathic nephrotic syndrome not only depend on treatment regimens and therapy responsiveness, but also on regional circumstances, lifestyles and living conditions. References 1. Foster BJ, Shults J, Zemel BS, Leonard MB (2006) Risk factors for glucocorticoid-induced obesity in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 21:973-980 2. Rüth E-M, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202-207 3. Hegarty J, Mughal MZ, Adams J, Webb NJA (2005) Reduced bone mineral density in adults treated with high-dose corticosteroids for childhood nephrotic syndrome.

Effect of obesity on response to cardiovascular drugs in pediatric patients with renal disease

“…This is an expected result because of the nature of the disease and concomitant treatment with corticosteroids [17,31]. On the other hand, patients with urologic abnormalities had the lowest requirements for antihypertensive treatment.…”

“…Thus, a knowledge of the underlying kidney disease and its management can facilitate the prediction of the drug response. Nephrotic syndrome patients were more prone to have a reduced efficacy of antihypertensive medications, possibly explained by hypoalbuminemia-induced water retention, obesity, and corticosteroid therapy [17,19]. In contrast, hypertensive patients with urologic abnormalities are more likely to respond to medications because they do not have similar risk factors for resistance to therapy.…”

“…Obesity was not the only confounding variable; corticosteroid therapy was also associated with a reduced diastolic response to CCBs. Prednisone and methylprednisone are commonly prescribed drugs in a therapeutic program aimed controlling the progression of a number of kidney diseases or as immunosuppressants in renal transplant recipients [17,31]. Corticosteroids are known to antagonize the antihypertensive effects of drugs [19].…”

“…This association has been attributed to an inflammation-induced reduction in binding to L-type calcium channels [13,14] and a downregulation of calcium channel target protein [13]. This specific effect of inflammation is important because obesity and other inflammatory states are complications of many diseases, such as hypertension, angina and acute myocardial infarction, which may ultimately require CCB therapy [17][18][19]. As such, obesity may contribute to poor disease outcome [20].…”

The importance of a ‘cohort effect’ in comparisons of groups with glucocorticoid-induced obesity

“…We appreciate the thoughtful comments by Neuhaus et al [1] regarding our recent study of risk factors for glucocorticoid-induced obesity in children with steroid-sensitive nephrotic syndrome [2]. We agree that the prevalence of obesity in U.S. children with remote nephrotic syndrome likely demonstrates regional variation consistent with the prevalence of obesity in the general U.S. pediatric population.…”